Multiple sclerosis (MS) is a serious human demyelination disease. Persistence infection of certain strains of TMEV results in a late demyelination disease in mice very similar to MS. We identified critical regions and found evidence to suggest that the persistence determinants are related to virus' ability to bind a host cellular receptor fragment, a sialyloligosaccharide. Our data showed that a persistent TMEV strain (BeAn) binds to sialyloligosaccharides while a non-persistent strain (GDVII) does not. This could imply that the persistent strains could recognize the sialylated receptors present on the glial cells to cause persistent infections, but the nonpersistent strains do not.